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CHAPTER 9 | CELL COMMUNICATION 253
9 | CELL
COMMUNICATION
Figure 9.1 Have you ever become separated from a friend while in a crowd? If so, you know the
challenge of searching for someone when surrounded by thousands of other people. If you and
your friend have cell phones, your chances of finding each other are good. A cell phone’s ability to
send and receive messages makes it an ideal communication device. (credit: modification of work
by Vincent and Bella Productions)
Chapter Outline
9.1: Signaling Molecules and Cellular Receptors
9.2: Propagation of the Signal
9.3: Response to the Signal
9.4: Signaling in Single-Celled Organisms
Introduction
Imagine what life would be like if you and the people around you could not communicate. You would
not be able to express your wishes to others, nor could you ask questions to find out more about your
environment. Social organization is dependent on communication between the individuals that comprise
that society; without communication, society would fall apart.
As with people, it is vital for individual cells to be able to interact with their environment. This is true
whether a cell is growing by itself in a pond or is one of many cells that form a larger organism. In order
to properly respond to external stimuli, cells have developed complex mechanisms of communication
that can receive a message, transfer the information across the plasma membrane, and then produce
changes within the cell in response to the message.
In multicellular organisms, cells send and receive chemical messages constantly to coordinate the actions
of distant organs, tissues, and cells. The ability to send messages quickly and efficiently enables cells to
coordinate and fine-tune their functions.
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While the necessity for cellular communication in larger organisms seems obvious, even single-celled
organisms communicate with each other. Yeast cells signal each other to aid mating. Some forms of
bacteria coordinate their actions in order to form large complexes called biofilms or to organize the
production of toxins to remove competing organisms. The ability of cells to communicate through
chemical signals originated in single cells and was essential for the evolution of multicellular organisms.
The efficient and error-free function of communication systems is vital for all life as we know it.
9.1 | Signaling Molecules and Cellular
Receptors
By the end of this section, you will be able to:
• Describe four types of signaling found in multicellular organisms
• Compare internal receptors with cell-surface receptors
• Recognize the relationship between a ligand’s structure and its mechanism of action
There are two kinds of communication in the world of living cells. Communication between cells is
called intercellular signaling, and communication within a cell is called intracellular signaling. An
easy way to remember the distinction is by understanding the Latin origin of the prefixes: inter- means
"between" (for example, intersecting lines are those that cross each other) and intra- means "inside" (like
intravenous).
Chemical signals are released by signaling cells in the form of small, usually volatile or soluble
molecules called ligands. A ligand is a molecule that binds another specific molecule, in some cases,
delivering a signal in the process. Ligands can thus be thought of as signaling molecules. Ligands interact
with proteins in target cells, which are cells that are affected by chemical signals; these proteins are also
called receptors. Ligands and receptors exist in several varieties; however, a specific ligand will have a
specific receptor that typically binds only that ligand.
Forms of Signaling
There are four categories of chemical signaling found in multicellular organisms: paracrine signaling,
endocrine signaling, autocrine signaling, and direct signaling across gap junctions (Figure 9.2). The
main difference between the different categories of signaling is the distance that the signal travels
through the organism to reach the target cell. Not all cells are affected by the same signals.
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CHAPTER 9 | CELL COMMUNICATION 255
Figure 9.2 In chemical signaling, a cell may target itself (autocrine signaling), a cell connected by
gap junctions, a nearby cell (paracrine signaling), or a distant cell (endocrine signaling). Paracrine
signaling acts on nearby cells, endocrine signaling uses the circulatory system to transport ligands,
and autocrine signaling acts on the signaling cell. Signaling via gap junctions involves signaling
molecules moving directly between adjacent cells.
Paracrine Signaling
Signals that act locally between cells that are close together are called paracrine signals. Paracrine
signals move by diffusion through the extracellular matrix. These types of signals usually elicit quick
responses that last only a short amount of time. In order to keep the response localized, paracrine ligand
molecules are normally quickly degraded by enzymes or removed by neighboring cells. Removing the
signals will reestablish the concentration gradient for the signal, allowing them to quickly diffuse through
the intracellular space if released again.
One example of paracrine signaling is the transfer of signals across synapses between nerve cells. A
nerve cell consists of a cell body, several short, branched extensions called dendrites that receive stimuli,
and a long extension called an axon, which transmits signals to other nerve cells or muscle cells. The
junction between nerve cells where signal transmission occurs is called a synapse. A synaptic signal is
a chemical signal that travels between nerve cells. Signals within the nerve cells are propagated by fastmoving electrical impulses. When these impulses reach the end of the axon, the signal continues on to a
dendrite of the next cell by the release of chemical ligands called neurotransmitters by the presynaptic
cell (the cell emitting the signal). The neurotransmitters are transported across the very small distances
between nerve cells, which are called chemical synapses (Figure 9.3). The small distance between nerve
cells allows the signal to travel quickly; this enables an immediate response, such as, Take your hand off
the stove!
When the neurotransmitter binds the receptor on the surface of the postsynaptic cell, the electrochemical
potential of the target cell changes, and the next electrical impulse is launched. The neurotransmitters
that are released into the chemical synapse are degraded quickly or get reabsorbed by the presynaptic
cell so that the recipient nerve cell can recover quickly and be prepared to respond rapidly to the next
synaptic signal.
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Figure 9.3 The distance between the presynaptic cell and the postsynaptic cell—called the synaptic
gap—is very small and allows for rapid diffusion of the neurotransmitter. Enzymes in the synapatic
cleft degrade some types of neurotransmitters to terminate the signal.
Endocrine Signaling
Signals from distant cells are called endocrine signals, and they originate from endocrine cells. (In the
body, many endocrine cells are located in endocrine glands, such as the thyroid gland, the hypothalamus,
and the pituitary gland.) These types of signals usually produce a slower response but have a longerlasting effect. The ligands released in endocrine signaling are called hormones, signaling molecules that
are produced in one part of the body but affect other body regions some distance away.
Hormones travel the large distances between endocrine cells and their target cells via the bloodstream,
which is a relatively slow way to move throughout the body. Because of their form of transport,
hormones get diluted and are present in low concentrations when they act on their target cells. This is
different from paracrine signaling, in which local concentrations of ligands can be very high.
Autocrine Signaling
Autocrine signals are produced by signaling cells that can also bind to the ligand that is released. This
means the signaling cell and the target cell can be the same or a similar cell (the prefix auto- means self,
a reminder that the signaling cell sends a signal to itself). This type of signaling often occurs during the
early development of an organism to ensure that cells develop into the correct tissues and take on the
proper function. Autocrine signaling also regulates pain sensation and inflammatory responses. Further,
if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing
the virus in the process. In some cases, neighboring cells of the same type are also influenced by the
released ligand. In embryological development, this process of stimulating a group of neighboring cells
may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper
developmental outcome.
Direct Signaling Across Gap Junctions
Gap junctions in animals and plasmodesmata in plants are connections between the plasma membranes
of neighboring cells. These water-filled channels allow small signaling molecules, called intracellular
mediators, to diffuse between the two cells. Small molecules, such as calcium ions (Ca2+), are able to
move between cells, but large molecules like proteins and DNA cannot fit through the channels. The
specificity of the channels ensures that the cells remain independent but can quickly and easily transmit
signals. The transfer of signaling molecules communicates the current state of the cell that is directly
next to the target cell; this allows a group of cells to coordinate their response to a signal that only one of
them may have received. In plants, plasmodesmata are ubiquitous, making the entire plant into a giant,
communication network.
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CHAPTER 9 | CELL COMMUNICATION 257
Types of Receptors
Receptors are protein molecules in the target cell or on its surface that bind ligand. There are two types
of receptors, internal receptors and cell-surface receptors.
Internal receptors
Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of
the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane.
Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis
(transcription) to mediate gene expression. Gene expression is the cellular process of transforming the
information in a cell's DNA into a sequence of amino acids, which ultimately forms a protein. When
the ligand binds to the internal receptor, a conformational change is triggered that exposes a DNAbinding site on the protein. The ligand-receptor complex moves into the nucleus, then binds to specific
regulatory regions of the chromosomal DNA and promotes the initiation of transcription (Figure 9.4).
Transcription is the process of copying the information in a cells DNA into a special form of RNA called
messenger RNA (mRNA); the cell uses information in the mRNA (which moves out into the cytoplasm
and associates with ribosomes) to link specific amino acids in the correct order, producing a protein.
Internal receptors can directly influence gene expression without having to pass the signal on to other
receptors or messengers.
Figure 9.4 Hydrophobic signaling molecules typically diffuse across the plasma membrane and
interact with intracellular receptors in the cytoplasm. Many intracellular receptors are transcription
factors that interact with DNA in the nucleus and regulate gene expression.
Cell-Surface Receptors
Cell-surface receptors, also known as transmembrane receptors, are cell surface, membrane-anchored
(integral) proteins that bind to external ligand molecules. This type of receptor spans the plasma
membrane and performs signal transduction, in which an extracellular signal is converted into an
intercellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they
affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to
individual cell types.
Because cell-surface receptor proteins are fundamental to normal cell functioning, it should come as no
surprise that a malfunction in any one of these proteins could have severe consequences. Errors in the
protein structures of certain receptor molecules have been shown to play a role in hypertension (high
blood pressure), asthma, heart disease, and cancer.
Each cell-surface receptor has three main components: an external ligand-binding domain, a hydrophobic
membrane-spanning region, and an intracellular domain inside the cell. The ligand-binding domain
is also called the extracellular domain. The size and extent of each of these domains vary widely,
depending on the type of receptor.
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How Viruses Recognize a Host
Unlike living cells, many viruses do not have a plasma membrane or any of the structures
necessary to sustain life. Some viruses are simply composed of an inert protein shell
containing DNA or RNA. To reproduce, viruses must invade a living cell, which serves as
a host, and then take over the hosts cellular apparatus. But how does a virus recognize its
host?
Viruses often bind to cell-surface receptors on the host cell. For example, the virus that
causes human influenza (flu) binds specifically to receptors on membranes of cells of the
respiratory system. Chemical differences in the cell-surface receptors among hosts mean
that a virus that infects a specific species (for example, humans) cannot infect another
species (for example, chickens).
However, viruses have very small amounts of DNA or RNA compared to humans, and,
as a result, viral reproduction can occur rapidly. Viral reproduction invariably produces
errors that can lead to changes in newly produced viruses; these changes mean that the
viral proteins that interact with cell-surface receptors may evolve in such a way that they
can bind to receptors in a new host. Such changes happen randomly and quite often in
the reproductive cycle of a virus, but the changes only matter if a virus with new binding
properties comes into contact with a suitable host. In the case of influenza, this situation
can occur in settings where animals and people are in close contact, such as poultry and
[1]
swine farms. Once a virus jumps to a new host, it can spread quickly. Scientists watch
newly appearing viruses (called emerging viruses) closely in the hope that such monitoring
can reduce the likelihood of global viral epidemics.
Cell-surface receptors are involved in most of the signaling in multicellular organisms. There are three
general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors,
and enzyme-linked receptors.
Ion channel-linked receptors bind a ligand and open a channel through the membrane that allows
specific ions to pass through. To form a channel, this type of cell-surface receptor has an extensive
membrane-spanning region. In order to interact with the phospholipid fatty acid tails that form the center
of the plasma membrane, many of the amino acids in the membrane-spanning region are hydrophobic
in nature. Conversely, the amino acids that line the inside of the channel are hydrophilic to allow for
the passage of water or ions. When a ligand binds to the extracellular region of the channel, there is a
conformational change in the proteins structure that allows ions such as sodium, calcium, magnesium,
and hydrogen to pass through (Figure 9.5).
Figure 9.5 Gated ion channels form a pore through the plasma membrane that opens when the
signaling molecule binds. The open pore then allows ions to flow into or out of the cell.
G-protein-linked receptors bind a ligand and activate a membrane protein called a G-protein. The
activated G-protein then interacts with either an ion channel or an enzyme in the membrane (Figure
1. A. B. Sigalov, The School of Nature. IV. Learning from Viruses, Self/Nonself 1, no. 4 (2010): 282-298. Y. Cao, X.
Koh, L. Dong, X. Du, A. Wu, X. Ding, H. Deng, Y. Shu, J. Chen, T. Jiang, Rapid Estimation of Binding Activity of
Influenza Virus Hemagglutinin to Human and Avian Receptors, PLoS One 6, no. 4 (2011): e18664.
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CHAPTER 9 | CELL COMMUNICATION 259
9.6). All G-protein-linked receptors have seven transmembrane domains, but each receptor has its own
specific extracellular domain and G-protein-binding site.
Cell signaling using G-protein-linked receptors occurs as a cyclic series of events. Before the ligand
binds, the inactive G-protein can bind to a newly revealed site on the receptor specific for its binding.
Once the G-protein binds to the receptor, the resultant shape change activates the G-protein, which
releases GDP and picks up GTP. The subunits of the G-protein then split into the α subunit and the βγ
subunit. One or both of these G-protein fragments may be able to activate other proteins as a result. After
awhile, the GTP on the active α subunit of the G-protein is hydrolyzed to GDP and the βγ subunit is
deactivated. The subunits reassociate to form the inactive G-protein and the cycle begins anew.
Figure 9.6 Heterotrimeric G proteins have three subunits: α, β, and γ. When a signaling molecule
binds to a G-protein-coupled receptor in the plasma membrane, a GDP molecule associated with the
α subunit is exchanged for GTP. The β and γ subunits dissociate from the α subunit, and a cellular
response is triggered either by the α subunit or the dissociated βγ pair. Hydrolysis of GTP to GDP
terminates the signal.
G-protein-linked receptors have been extensively studied and much has been learned about their roles in
maintaining health. Bacteria that are pathogenic to humans can release poisons that interrupt specific Gprotein-linked receptor function, leading to illnesses such as pertussis, botulism, and cholera. In cholera
(Figure 9.7), for example, the water-borne bacterium Vibrio cholerae produces a toxin, choleragen, that
binds to cells lining the small intestine. The toxin then enters these intestinal cells, where it modifies a
G-protein that controls the opening of a chloride channel and causes it to remain continuously active,
resulting in large losses of fluids from the body and potentially fatal dehydration as a result.
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Figure 9.7 Transmitted primarily through contaminated drinking water, cholera is a major cause of
death in the developing world and in areas where natural disasters interrupt the availability of clean
water. The cholera bacterium, Vibrio cholerae, creates a toxin that modifies G-protein-mediated cell
signaling pathways in the intestines. Modern sanitation eliminates the threat of cholera outbreaks,
such as the one that swept through New York City in 1866. This poster from that era shows how,
at that time, the way that the disease was transmitted was not understood. (credit: New York City
Sanitary Commission)
Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with
an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme. Other enzymelinked receptors have a small intracellular domain that interacts directly with an enzyme. The enzymelinked receptors normally have large extracellular and intracellular domains, but the membrane-spanning
region consists of a single alpha-helical region of the peptide strand. When a ligand binds to the
extracellular domain, a signal is transferred through the membrane, activating the enzyme. Activation of
the enzyme sets off a chain of events within the cell that eventually leads to a response. One example
of this type of enzyme-linked receptor is the tyrosine kinase receptor (Figure 9.8). A kinase is an
enzyme that transfers phosphate groups from ATP to another protein. The tyrosine kinase receptor
transfers phosphate groups to tyrosine molecules (tyrosine residues). First, signaling molecules bind to
the extracellular domain of two nearby tyrosine kinase receptors. The two neighboring receptors then
bond together, or dimerize. Phosphates are then added to tyrosine residues on the intracellular domain
of the receptors (phosphorylation). The phosphorylated residues can then transmit the signal to the next
messenger within the cytoplasm.
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CHAPTER 9 | CELL COMMUNICATION 261
Figure 9.8 A receptor tyrosine kinase is an enzyme-linked receptor with a single
transmembrane region, and extracellular and intracellular domains. Binding of a signaling
molecule to the extracellular domain causes the receptor to dimerize. Tyrosine residues on the
intracellular domain are then autophosphorylated, triggering a downstream cellular response.
The signal is terminated by a phosphatase that removes the phosphates from the
phosphotyrosine residues.
HER2 is a receptor tyrosine kinase. In 30 percent of human breast cancers, HER2 is
permanently activated, resulting in unregulated cell division. Lapatinib, a drug used to treat
breast cancer, inhibits HER2 receptor tyrosine kinase autophosphorylation (the process by
which the receptor adds phosphates onto itself), thus reducing tumor growth by 50 percent.
Besides autophosphorylation, which of the following steps would be inhibited by Lapatinib?
a. Signaling molecule binding, dimerization, and the downstream cellular response
b. Dimerization, and the downstream cellular response
c. The downstream cellular response
d. Phosphatase activity, dimerization, and the downsteam cellular response
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Signaling Molecules
Produced by signaling cells and the subsequent binding to receptors in target cells, ligands act as
chemical signals that travel to the target cells to coordinate responses. The types of molecules that serve
as ligands are incredibly varied and range from small proteins to small ions like calcium (Ca2+).
Small Hydrophobic Ligands
Small hydrophobic ligands can directly diffuse through the plasma membrane and interact with internal
receptors. Important members of this class of ligands are the steroid hormones. Steroids are lipids
that have a hydrocarbon skeleton with four fused rings; different steroids have different functional
groups attached to the carbon skeleton. Steroid hormones include the female sex hormone, estradiol,
which is a type of estrogen; the male sex hormone, testosterone; and cholesterol, which is an important
structural component of biological membranes and a precursor of steriod hormones (Figure 9.9).
Other hydrophobic hormones include thyroid hormones and vitamin D. In order to be soluble in
blood, hydrophobic ligands must bind to carrier proteins while they are being transported through the
bloodstream.
Figure 9.9 Steroid hormones have similar chemical structures to their precursor, cholesterol.
Because these molecules are small and hydrophobic, they can diffuse directly across the plasma
membrane into the cell, where they interact with internal receptors.
Water-Soluble Ligands
Water-soluble ligands are polar and therefore cannot pass through the plasma membrane unaided;
sometimes, they are too large to pass through the membrane at all. Instead, most water-soluble ligands
bind to the extracellular domain of cell-surface receptors. This group of ligands is quite diverse and
includes small molecules, peptides, and proteins.
Other Ligands
Nitric oxide (NO) is a gas that also acts as a ligand. It is able to diffuse directly across the plasma
membrane, and one of its roles is to interact with receptors in smooth muscle and induce relaxation of
the tissue. NO has a very short half-life and therefore only functions over short distances. Nitroglycerin,
a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate
(expand), thus restoring blood flow to the heart. NO has become better known recently because the
pathway that it affects is targeted by prescription medications for erectile dysfunction, such as Viagra
(erection involves dilated blood vessels).
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9.2 | Propagation of the Signal
By the end of this section, you will be able to:
• Explain how the binding of a ligand initiates signal transduction throughout a cell
• Recognize the role of phosphorylation in the transmission of intracellular signals
• Evaluate the role of second messengers in signal transmission
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm.
Continuation of a signal in this manner is called signal transduction. Signal transduction only occurs
with cell-surface receptors because internal receptors are able to interact directly with DNA in the
nucleus to initiate protein synthesis.
When a ligand binds to its receptor, conformational changes occur that affect the receptor’s intracellular
domain. Conformational changes of the extracellular domain upon ligand binding can propagate through
the membrane region of the receptor and lead to activation of the intracellular domain or its associated
proteins. In some cases, binding of the ligand causes dimerization of the receptor, which means that two
receptors bind to each other to form a stable complex called a dimer. A dimer is a chemical compound
formed when two molecules (often identical) join together. The binding of the receptors in this manner
enables their intracellular domains to come into close contact and activate each other.
Binding Initiates a Signaling Pathway
After the ligand binds to the cell-surface receptor, the activation of the receptor’s intracellular
components sets off a chain of events that is called a signaling pathway or a signaling cascade. In a
signaling pathway, second messengers, enzymes, and activated proteins interact with specific proteins,
which are in turn activated in a chain reaction that eventually leads to a change in the cell’s environment
(Figure 9.10). The events in the cascade occur in a series, much like a current flows in a river.
Interactions that occur before a certain point are defined as upstream events, and events after that point
are called downstream events.
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Figure 9.10 The epidermal growth factor (EGF) receptor (EGFR) is a receptor tyrosine kinase
involved in the regulation of cell growth, wound healing, and tissue repair. When EGF binds to
the EGFR, a cascade of downstream events causes the cell to grow and divide. If EGFR is
activated at inappropriate times, uncontrolled cell growth (cancer) may occur.
In certain cancers, the GTPase activity of the RAS G-protein is inhibited. This means that
the RAS protein can no longer hydrolyze GTP into GDP. What effect would this have on
downstream cellular events?
Signaling pathways can get very complicated very quickly because most cellular proteins can affect
different downstream events, depending on the conditions within the cell. A single pathway can branch
off toward different endpoints based on the interplay between two or more signaling pathways, and the
same ligands are often used to initiate different signals in different cell types. This variation in response
is due to differences in protein expression in different cell types. Another complicating element is signal
integration of the pathways, in which signals from two or more different cell-surface receptors merge
to activate the same response in the cell. This process can ensure that multiple external requirements are
met before a cell commits to a specific response.
The effects of extracellular signals can also be amplified by enzymatic cascades. At the initiation of the
signal, a single ligand binds to a single receptor. However, activation of a receptor-linked enzyme can
activate many copies of a component of the signaling cascade, which amplifies the signal.
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CHAPTER 9 | CELL COMMUNICATION 265
Methods of Intracellular Signaling
The induction of a signaling pathway depends on the modification of a cellular component by an enzyme.
There are numerous enzymatic modifications that can occur, and they are recognized in turn by the next
component downstream. The following are some of the more common events in intracellular signaling.
Observe an animation of cell signaling at this site (http://openstaxcollege.org/l/cell_signals) .
Phosphorylation
One of the most common chemical modifications that occurs in signaling pathways is the addition of
–3
a phosphate group (PO4 ) to a molecule such as a protein in a process called phosphorylation. The
phosphate can be added to a nucleotide such as GMP to form GDP or GTP. Phosphates are also often
added to serine, threonine, and tyrosine residues of proteins, where they replace the hydroxyl group
of the amino acid (Figure 9.11). The transfer of the phosphate is catalyzed by an enzyme called a
kinase. Various kinases are named for the substrate they phosphorylate. Phosphorylation of serine and
threonine residues often activates enzymes. Phosphorylation of tyrosine residues can either affect the
activity of an enzyme or create a binding site that interacts with downstream components in the signaling
cascade. Phosphorylation may activate or inactivate enzymes, and the reversal of phosphorylation,
dephosphorylation by a phosphatase, will reverse the effect.
Figure 9.11 In protein phosphorylation, a phosphate group (PO4-3 ) is added to residues of the
amino acids serine, threonine, and tyrosine.
Second Messengers
Second messengers are small molecules that propagate a signal after it has been initiated by the binding
of the signaling molecule to the receptor. These molecules help to spread a signal through the cytoplasm
by altering the behavior of certain cellular proteins.
Calcium ion is a widely used second messenger. The free concentration of calcium ions (Ca2+) within a
cell is very low because ion pumps in the plasma membrane continuously use adenosine-5'-triphosphate
(ATP) to remove it. For signaling purposes, Ca2+ is stored in cytoplasmic vesicles, such as the
266 CHAPTER 9 | CELL COMMUNICATION
endoplasmic reticulum, or accessed from outside the cell. When signaling occurs, ligand-gated calcium
ion channels allow the higher levels of Ca2+ that are present outside the cell (or in intracellular storage
compartments) to flow into the cytoplasm, which raises the concentration of cytoplasmic Ca2+. The
response to the increase in Ca2+ varies, depending on the cell type involved. For example, in the β-cells
of the pancreas, Ca2+ signaling leads to the release of insulin, and in muscle cells, an increase in Ca2+
leads to muscle contractions.
Another second messenger utilized in many different cell types is cyclic AMP (cAMP). Cyclic AMP is
synthesized by the enzyme adenylyl cyclase from ATP (Figure 9.12). The main role of cAMP in cells is
to bind to and activate an enzyme called cAMP-dependent kinase (A-kinase). A-kinase regulates many
vital metabolic pathways: It phosphorylates serine and threonine residues of its target proteins, activating
them in the process. A-kinase is found in many different types of cells, and the target proteins in each
kind of cell are different. Differences give rise to the variation of the responses to cAMP in different
cells.
Figure 9.12 This diagram shows the mechanism for the formation of cyclic AMP (cAMP). cAMP
serves as a second messenger to activate or inactivate proteins within the cell. Termination of the
signal occurs when an enzyme called phosphodiesterase converts cAMP into AMP.
Present in small concentrations in the plasma membrane, inositol phospholipids are lipids that can also
be converted into second messengers. Because these molecules are membrane components, they are
located near membrane-bound receptors and can easily interact with them. Phosphatidylinositol (PI) is
the main phospholipid that plays a role in cellular signaling. Enzymes known as kinases phosphorylate
PI to form PI-phosphate (PIP) and PI-bisphosphate (PIP2).
The enzyme phospholipase C cleaves PIP2 to form diacylglycerol (DAG) and inositol triphosphate
(IP3) (Figure 9.13). These products of the cleavage of PIP2 serve as second messengers. Diacylglycerol
(DAG) remains in the plasma membrane and activates protein kinase C (PKC), which then
phosphorylates serine and threonine residues in its target proteins. IP3 diffuses into the cytoplasm and
binds to ligand-gated calcium channels in the endoplasmic reticulum to release Ca2+ that continues the
signal cascade.
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CHAPTER 9 | CELL COMMUNICATION 267
Figure 9.13 The enzyme phospholipase C breaks down PIP2 into IP3 and DAG, both of which serve
as second messengers.
9.3 | Response to the Signal
By the end of this section, you will be able to:
• Describe how signaling pathways direct protein expression, cellular metabolism, and cell
growth
• Identify the function of PKC in signal transduction pathways
• Recognize the role of apoptosis in the development and maintenance of a healthy organism
Inside the cell, ligands bind to their internal receptors, allowing them to directly affect the cell’s DNA and
protein-producing machinery. Using signal transduction pathways, receptors in the plasma membrane
produce a variety of effects on the cell. The results of signaling pathways are extremely varied and
depend on the type of cell involved as well as the external and internal conditions. A small sampling of
responses is described below.
Gene Expression
Some signal transduction pathways regulate the transcription of RNA. Others regulate the translation of
proteins from mRNA. An example of a protein that regulates translation in the nucleus is the MAP kinase
ERK. ERK is activated in a phosphorylation cascade when epidermal growth factor (EGF) binds the
EGF receptor (see Figure 9.10). Upon phosphorylation, ERK enters the nucleus and activates a protein
kinase that, in turn, regulates protein translation (Figure 9.14).
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Figure 9.14 ERK is a MAP kinase that activates translation when it is phosphorylated. ERK
phosphorylates MNK1, which in turn phosphorylates eIF-4E, an elongation initiation factor that, with
other initiation factors, is associated with mRNA. When eIF-4E becomes phosphorylated, the mRNA
unfolds, allowing protein synthesis in the nucleus to begin. (See Figure 9.10 for the phosphorylation
pathway that activates ERK.)
The second kind of protein with which PKC can interact is a protein that acts as an inhibitor. An
inhibitor is a molecule that binds to a protein and prevents it from functioning or reduces its function.
In this case, the inhibitor is a protein called Iκ-B, which binds to the regulatory protein NF-κB. (The
symbol κ represents the Greek letter kappa.) When Iκ-B is bound to NF-κB, the complex cannot enter
the nucleus of the cell, but when Iκ-B is phosphorylated by PKC, it can no longer bind NF-κB, and NFκB (a transcription factor) can enter the nucleus and initiate RNA transcription. In this case, the effect of
phosphorylation is to inactivate an inhibitor and thereby activate the process of transcription.
Increase in Cellular Metabolism
The result of another signaling pathway affects muscle cells. The activation of β-adrenergic receptors
in muscle cells by adrenaline leads to an increase in cyclic AMP (cAMP) inside the cell. Also known
as epinephrine, adrenaline is a hormone (produced by the adrenal gland attached to the kidney) that
readies the body for short-term emergencies. Cyclic AMP activates PKA (protein kinase A), which in
turn phosphorylates two enzymes. The first enzyme promotes the degradation of glycogen by activating
intermediate glycogen phosphorylase kinase (GPK) that in turn activates glycogen phosphorylase (GP)
that catabolizes glycogen into glucose. (Recall that your body converts excess glucose to glycogen for
short-term storage. When energy is needed, glycogen is quickly reconverted to glucose.) Phosphorylation
of the second enzyme, glycogen synthase (GS), inhibits its ability to form glycogen from glucose. In
this manner, a muscle cell obtains a ready pool of glucose by activating its formation via glycogen
degradation and by inhibiting the use of glucose to form glycogen, thus preventing a futile cycle of
glycogen degradation and synthesis. The glucose is then available for use by the muscle cell in response
to a sudden surge of adrenaline—the “fight or flight” reflex.
Cell Growth
Cell signaling pathways also play a major role in cell division. Cells do not normally divide unless
they are stimulated by signals from other cells. The ligands that promote cell growth are called growth
factors. Most growth factors bind to cell-surface receptors that are linked to tyrosine kinases. These cellsurface receptors are called receptor tyrosine kinases (RTKs). Activation of RTKs initiates a signaling
pathway that includes a G-protein called RAS, which activates the MAP kinase pathway described
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CHAPTER 9 | CELL COMMUNICATION 269
earlier. The enzyme MAP kinase then stimulates the expression of proteins that interact with other
cellular components to initiate cell division.
Cancer Biologist
Cancer biologists study the molecular origins of cancer with the goal of developing new
prevention methods and treatment strategies that will inhibit the growth of tumors without
harming the normal cells of the body. As mentioned earlier, signaling pathways control
cell growth. These signaling pathways are controlled by signaling proteins, which are, in
turn, expressed by genes. Mutations in these genes can result in malfunctioning signaling
proteins. This prevents the cell from regulating its cell cycle, triggering unrestricted cell
division and cancer. The genes that regulate the signaling proteins are one type of
oncogene which is a gene that has the potential to cause cancer. The gene encoding RAS
is an oncogene that was originally discovered when mutations in the RAS protein were
linked to cancer. Further studies have indicated that 30 percent of cancer cells have a
mutation in the RAS gene that leads to uncontrolled growth. If left unchecked, uncontrolled
cell division can lead tumor formation and metastasis, the growth of cancer cells in new
locations in the body.
Cancer biologists have been able to identify many other oncogenes that contribute to the
development of cancer. For example, HER2 is a cell-surface receptor that is present in
excessive amounts in 20 percent of human breast cancers. Cancer biologists realized
that gene duplication led to HER2 overexpression in 25 percent of breast cancer patients
and developed a drug called Herceptin (trastuzumab). Herceptin is a monoclonal antibody
that targets HER2 for removal by the immune system. Herceptin therapy helps to control
signaling through HER2. The use of Herceptin in combination with chemotherapy has
helped to increase the overall survival rate of patients with metastatic breast cancer.
More information on cancer biology research can be found at the National Cancer Institute
website (http://www.cancer.gov/cancertopics/understandingcancer/targetedtherapies).
Cell Death
When a cell is damaged, superfluous, or potentially dangerous to an organism, a cell can initiate a
mechanism to trigger programmed cell death, or apoptosis. Apoptosis allows a cell to die in a controlled
manner that prevents the release of potentially damaging molecules from inside the cell. There are many
internal checkpoints that monitor a cell’s health; if abnormalities are observed, a cell can spontaneously
initiate the process of apoptosis. However, in some cases, such as a viral infection or uncontrolled cell
division due to cancer, the cell’s normal checks and balances fail. External signaling can also initiate
apoptosis. For example, most normal animal cells have receptors that interact with the extracellular
matrix, a network of glycoproteins that provides structural support for cells in an organism. The binding
of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell. However, if
the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis.
This system keeps cells from traveling through the body and proliferating out of control, as happens with
tumor cells that metastasize.
Another example of external signaling that leads to apoptosis occurs in T-cell development. T-cells are
immune cells that bind to foreign macromolecules and particles, and target them for destruction by the
immune system. Normally, T-cells do not target “self” proteins (those of their own organism), a process
that can lead to autoimmune diseases. In order to develop the ability to discriminate between self and
non-self, immature T-cells undergo screening to determine whether they bind to so-called self proteins. If
the T-cell receptor binds to self proteins, the cell initiates apoptosis to remove the potentially dangerous
cell.
Apoptosis is also essential for normal embryological development. In vertebrates, for example, early
stages of development include the formation of web-like tissue between individual fingers and toes
(Figure 9.15). During the course of normal development, these unneeded cells must be eliminated,
enabling fully separated fingers and toes to form. A cell signaling mechanism triggers apoptosis, which
destroys the cells between the developing digits.
270 CHAPTER 9 | CELL COMMUNICATION
Figure 9.15 The histological section of a foot of a 15-day-old mouse embryo, visualized using light
microscopy, reveals areas of tissue between the toes, which apoptosis will eliminate before the
mouse reaches its full gestational age at 27 days. (credit: modification of work by Michal Mañas)
Termination of the Signal Cascade
The aberrant signaling often seen in tumor cells is proof that the termination of a signal at the appropriate
time can be just as important as the initiation of a signal. One method of stopping a specific signal is to
degrade the ligand or remove it so that it can no longer access its receptor. One reason that hydrophobic
hormones like estrogen and testosterone trigger long-lasting events is because they bind carrier proteins.
These proteins allow the insoluble molecules to be soluble in blood, but they also protect the hormones
from degradation by circulating enzymes.
Inside the cell, many different enzymes reverse the cellular modifications that result from signaling
cascades. For example, phosphatases are enzymes that remove the phosphate group attached to proteins
by kinases in a process called dephosphorylation. Cyclic AMP (cAMP) is degraded into AMP by
phosphodiesterase, and the release of calcium stores is reversed by the Ca2+ pumps that are located in
the external and internal membranes of the cell.
9.4 | Signaling in Single-Celled Organisms
By the end of this section, you will be able to:
• Describe how single-celled yeasts use cell signaling to communicate with one another
• Relate the role of quorum sensing to the ability of some bacteria to form biofilms
Within-cell signaling allows bacteria to respond to environmental cues, such as nutrient levels, some
single-celled organisms also release molecules to signal to each other.
Signaling in Yeast
Yeasts are eukaryotes (fungi), and the components and processes found in yeast signals are similar to
those of cell-surface receptor signals in multicellular organisms. Budding yeasts (Figure 9.16) are able
to participate in a process that is similar to sexual reproduction that entails two haploid cells (cells with
one-half the normal number of chromosomes) combining to form a diploid cell (a cell with two sets of
each chromosome, which is what normal body cells contain). In order to find another haploid yeast cell
that is prepared to mate, budding yeasts secrete a signaling molecule called mating factor. When mating
factor binds to cell-surface receptors in other yeast cells that are nearby, they stop their normal growth
cycles and initiate a cell signaling cascade that includes protein kinases and GTP-binding proteins that
are similar to G-proteins.
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CHAPTER 9 | CELL COMMUNICATION 271
Figure 9.16 Budding Saccharomyces cerevisiae yeast cells can communicate by releasing a
signaling molecule called mating factor. In this micrograph, they are visualized using differential
interference contrast microscopy, a light microscopy technique that enhances the contrast of the
sample.
Signaling in Bacteria
Signaling in bacteria enables bacteria to monitor extracellular conditions, ensure that there are sufficient
amounts of nutrients, and ensure that hazardous situations are avoided. There are circumstances,
however, when bacteria communicate with each other.
The first evidence of bacterial communication was observed in a bacterium that has a symbiotic
relationship with Hawaiian bobtail squid. When the population density of the bacteria reaches a certain
level, specific gene expression is initiated, and the bacteria produce bioluminescent proteins that emit
light. Because the number of cells present in the environment (cell density) is the determining factor
for signaling, bacterial signaling was named quorum sensing. In politics and business, a quorum is the
minimum number of members required to be present to vote on an issue.
Quorum sensing uses autoinducers as signaling molecules. Autoinducers are signaling molecules
secreted by bacteria to communicate with other bacteria of the same kind. The secreted autoinducers
can be small, hydrophobic molecules such as acyl-homoserine lactone, (AHL) or larger peptide-based
molecules; each type of molecule has a different mode of action. When AHL enters target bacteria,
it binds to transcription factors, which then switch gene expression on or off (Figure 9.17). The
peptide autoinducers stimulate more complicated signaling pathways that include bacterial kinases. The
changes in bacteria following exposure to autoinducers can be quite extensive. The pathogenic bacterium
Pseudomonas aeruginosa has 616 different genes that respond to autoinducers.
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Figure 9.17 Autoinducers are small molecules or proteins produced by bacteria that regulate
gene expression.
Which of the following statements about quorum sensing is false?
a. Autoinducer must bind to receptor to turn on transcription of genes responsible for the
production of more autoinducer.
b. The receptor stays in the bacterial cell, but the autoinducer diffuses out.
c. Autoinducer can only act on a different cell: it cannot act on the cell in which it is made.
d. Autoinducer turns on genes that enable the bacteria to form a biofilm.
Some species of bacteria that use quorum sensing form biofilms, complex colonies of bacteria (often
containing several species) that exchange chemical signals to coordinate the release of toxins that will
attack the host. Bacterial biofilms (Figure 9.18) can sometimes be found on medical equipment; when
biofilms invade implants such as hip or knee replacements or heart pacemakers, they can cause lifethreatening infections.
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CHAPTER 9 | CELL COMMUNICATION 273
Figure 9.18 Cell-cell communication enables these (a) Staphylococcus aureus bacteria to
work together to form a biofilm inside a hospital patient’s catheter, seen here via scanning
electron microscopy. S. aureus is the main cause of hospital-acquired infections. (b) Hawaiian
bobtail squid have a symbiotic relationship with the bioluminescent bacteria Vibrio fischeri. The
luminescence makes it difficult to see the squid from below because it effectively eliminates its
shadow. In return for camouflage, the squid provides food for the bacteria. Free-living V. fischeri
do not produce luciferase, the enzyme responsible for luminescence, but V. fischeri living in
a symbiotic relationship with the squid do. Quorum sensing determines whether the bacteria
should produce the luciferase enzyme. (credit a: modifications of work by CDC/Janice Carr;
credit b: modifications of work by Cliff1066/Flickr)
What advantage might biofilm production confer on the S. aureus inside the catheter?
Research on the details of quorum sensing has led to advances in growing bacteria for industrial
purposes. Recent discoveries suggest that it may be possible to exploit bacterial signaling pathways to
control bacterial growth; this process could replace or supplement antibiotics that are no longer effective
in certain situations.
Watch geneticist Bonnie Bassler discuss her discovery (http://openstaxcollege.org/l/bacteria_talk)
of quorum sensing in biofilm bacteria in squid.
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Cellular Communication in Yeasts
The first life on our planet consisted of single-celled prokaryotic organisms that had
limited interaction with each other. While some external signaling occurs between different
species of single-celled organisms, the majority of signaling within bacteria and yeasts
concerns only other members of the same species. The evolution of cellular
communication is an absolute necessity for the development of multicellular organisms,
and this innovation is thought to have required approximately 2.5 billion years to appear in
early life forms.
Yeasts are single-celled eukaryotes, and therefore have a nucleus and organelles
characteristic of more complex life forms. Comparisons of the genomes of yeasts,
nematode worms, fruit flies, and humans illustrate the evolution of increasingly complex
signaling systems that allow for the efficient inner workings that keep humans and other
complex life forms functioning correctly.
Kinases are a major component of cellular communication, and studies of these enzymes
illustrate the evolutionary connectivity of different species. Yeasts have 130 types of
kinases. More complex organisms such as nematode worms and fruit flies have 454
and 239 kinases, respectively. Of the 130 kinase types in yeast, 97 belong to the 55
subfamilies of kinases that are found in other eukaryotic organisms. The only obvious
deficiency seen in yeasts is the complete absence of tyrosine kinases. It is hypothesized
that phosphorylation of tyrosine residues is needed to control the more sophisticated
functions of development, differentiation, and cellular communication used in multicellular
organisms.
Because yeasts contain many of the same classes of signaling proteins as humans, these
organisms are ideal for studying signaling cascades. Yeasts multiply quickly and are much
simpler organisms than humans or other multicellular animals. Therefore, the signaling
cascades are also simpler and easier to study, although they contain similar counterparts
[2]
to human signaling.
Watch this collection (http://openstaxcollege.org/l/bacteria_biofilm) of interview clips with biofilm
researchers in “What Are Bacterial Biofilms?”
2. G. Manning, G.D. Plowman, T. Hunter, S. Sudarsanam, “Evolution of Protein Kinase Signaling from Yeast to
Man,” Trends in Biochemical Sciences 27, no. 10 (2002): 514–520.
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CHAPTER 9 | CELL COMMUNICATION 275
KEY TERMS
apoptosis programmed cell death
autocrine signal signal that is sent and received by the same or similar nearby cells
autoinducer signaling molecule secreted by bacteria to communicate with other bacteria of its kind
and others
cell-surface receptor cell-surface protein that transmits a signal from the exterior of the cell to the
interior, even though the ligand does not enter the cell
chemical synapse small space between axon terminals and dendrites of nerve cells where
neurotransmitters function
cyclic AMP (cAMP) second messenger that is derived from ATP
cyclic AMP-dependent kinase (also, protein kinase A, or PKA) kinase that is activated by
binding to cAMP
diacylglycerol (DAG) cleavage product of PIP2 that is used for signaling within the plasma
membrane
dimer chemical compound formed when two molecules join together
dimerization (of receptor proteins) interaction of two receptor proteins to form a functional complex
called a dimer
endocrine cell cell that releases ligands involved in endocrine signaling (hormones)
endocrine signal long-distance signal that is delivered by ligands (hormones) traveling through an
organisms circulatory system from the signaling cell to the target cell
enzyme-linked receptor cell-surface receptor with intracellular domains that are associated with
membrane-bound enzymes
extracellular domain region of a cell-surface receptor that is located on the cell surface
G-protein-linked receptor cell-surface receptor that activates membrane-bound G-proteins to
transmit a signal from the receptor to nearby membrane components
growth factor ligand that binds to cell-surface receptors and stimulates cell growth
inhibitor molecule that binds to a protein (usually an enzyme) and keeps it from functioning
inositol phospholipid lipid present at small concentrations in the plasma membrane that is
converted into a second messenger; it has inositol (a carbohydrate) as its hydrophilic head group
inositol triphosphate (IP3) cleavage product of PIP2 that is used for signaling within the cell
intercellular signaling communication between cells
internal receptor (also, intracellular receptor) receptor protein that is located in the cytosol of a cell
and binds to ligands that pass through the plasma membrane
intracellular mediator (also, second messenger) small molecule that transmits signals within a cell
intracellular signaling communication within cells
ion channel-linked receptor cell-surface receptor that forms a plasma membrane channel, which
opens when a ligand binds to the extracellular domain (ligand-gated channels)
kinase enzyme that catalyzes the transfer of a phosphate group from ATP to another molecule
276 CHAPTER 9 | CELL COMMUNICATION
ligand molecule produced by a signaling cell that binds with a specific receptor, delivering a signal in
the process
mating factor signaling molecule secreted by yeast cells to communicate to nearby yeast cells that
they are available to mate and communicating their mating orientation
neurotransmitter chemical ligand that carries a signal from one nerve cell to the next
paracrine signal signal between nearby cells that is delivered by ligands traveling in the liquid
medium in the space between the cells
phosphatase enzyme that removes the phosphate group from a molecule that has been previously
phosphorylated
phosphodiesterase enzyme that degrades cAMP, producing AMP, to terminate signaling
quorum sensing method of cellular communication used by bacteria that informs them of the
abundance of similar (or different) bacteria in the environment
receptor protein in or on a target cell that bind to ligands
second messenger small, non-protein molecule that propagates a signal within the cell after
activation of a receptor causes its release
signal integration interaction of signals from two or more different cell-surface receptors that
merge to activate the same response in the cell
signal transduction propagation of the signal through the cytoplasm (and sometimes also the
nucleus) of the cell
signaling cell cell that releases signal molecules that allow communication with another cell
signaling pathway (also signaling cascade) chain of events that occurs in the cytoplasm of the cell
to propagate the signal from the plasma membrane to produce a response
synaptic signal chemical signal (neurotransmitter) that travels between nerve cells
target cell cell that has a receptor for a signal or ligand from a signaling cell
CHAPTER SUMMARY
9.1 Signaling Molecules and Cellular Receptors
Cells communicate by both inter- and intracellular signaling. Signaling cells secrete ligands that bind to
target cells and initiate a chain of events within the target cell. The four categories of signaling in
multicellular organisms are paracrine signaling, endocrine signaling, autocrine signaling, and direct
signaling across gap junctions. Paracrine signaling takes place over short distances. Endocrine signals
are carried long distances through the bloodstream by hormones, and autocrine signals are received by
the same cell that sent the signal or other nearby cells of the same kind. Gap junctions allow small
molecules, including signaling molecules, to flow between neighboring cells.
Internal receptors are found in the cell cytoplasm. Here, they bind ligand molecules that cross the
plasma membrane; these receptor-ligand complexes move to the nucleus and interact directly with
cellular DNA. Cell-surface receptors transmit a signal from outside the cell to the cytoplasm. Ion
channel-linked receptors, when bound to their ligands, form a pore through the plasma membrane
through which certain ions can pass. G-protein-linked receptors interact with a G-protein on the
cytoplasmic side of the plasma membrane, promoting the exchange of bound GDP for GTP and
interacting with other enzymes or ion channels to transmit a signal. Enzyme-linked receptors transmit a
signal from outside the cell to an intracellular domain of a membrane-bound enzyme. Ligand binding
causes activation of the enzyme. Small hydrophobic ligands (like steroids) are able to penetrate the
plasma membrane and bind to internal receptors. Water-soluble hydrophilic ligands are unable to pass
through the membrane; instead, they bind to cell-surface receptors, which transmit the signal to the
inside of the cell.
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CHAPTER 9 | CELL COMMUNICATION 277
9.2 Propagation of the Signal
Ligand binding to the receptor allows for signal transduction through the cell. The chain of events that
conveys the signal through the cell is called a signaling pathway or cascade. Signaling pathways are
often very complex because of the interplay between different proteins. A major component of cell
signaling cascades is the phosphorylation of molecules by enzymes known as kinases. Phosphorylation
adds a phosphate group to serine, threonine, and tyrosine residues in a protein, changing their shapes,
and activating or inactivating the protein. Small molecules like nucleotides can also be phosphorylated.
Second messengers are small, non-protein molecules that are used to transmit a signal within a cell.
Some examples of second messengers are calcium ions (Ca2+), cyclic AMP (cAMP), diacylglycerol
(DAG), and inositol triphosphate (IP3).
9.3 Response to the Signal
The initiation of a signaling pathway is a response to external stimuli. This response can take many
different forms, including protein synthesis, a change in the cell’s metabolism, cell growth, or even cell
death. Many pathways influence the cell by initiating gene expression, and the methods utilized are
quite numerous. Some pathways activate enzymes that interact with DNA transcription factors. Others
modify proteins and induce them to change their location in the cell. Depending on the status of the
organism, cells can respond by storing energy as glycogen or fat, or making it available in the form of
glucose. A signal transduction pathway allows muscle cells to respond to immediate requirements for
energy in the form of glucose. Cell growth is almost always stimulated by external signals called
growth factors. Uncontrolled cell growth leads to cancer, and mutations in the genes encoding protein
components of signaling pathways are often found in tumor cells. Programmed cell death, or apoptosis,
is important for removing damaged or unnecessary cells. The use of cellular signaling to organize the
dismantling of a cell ensures that harmful molecules from the cytoplasm are not released into the spaces
between cells, as they are in uncontrolled death, necrosis. Apoptosis also ensures the efficient recycling
of the components of the dead cell. Termination of the cellular signaling cascade is very important so
that the response to a signal is appropriate in both timing and intensity. Degradation of signaling
molecules and dephosphorylation of phosphorylated intermediates of the pathway by phosphatases are
two ways to terminate signals within the cell.
9.4 Signaling in Single-Celled Organisms
Yeasts and multicellular organisms have similar signaling mechanisms. Yeasts use cell-surface
receptors and signaling cascades to communicate information on mating with other yeast cells. The
signaling molecule secreted by yeasts is called mating factor.
Bacterial signaling is called quorum sensing. Bacteria secrete signaling molecules called autoinducers
that are either small, hydrophobic molecules or peptide-based signals. The hydrophobic autoinducers,
such as AHL, bind transcription factors and directly affect gene expression. The peptide-based
molecules bind kinases and initiate signaling cascades in the cells.
ART CONNECTION QUESTIONS
1. Figure 9.8 HER2 is a receptor tyrosine kinase.
In 30 percent of human breast cancers, HER2 is
permanently activated, resulting in unregulated
cell division. Lapatinib, a drug used to treat breast
cancer, inhibits HER2 receptor tyrosine kinase
autophosphorylation (the process by which the
receptor adds phosphates onto itself), thus
reducing tumor growth by 50 percent. Besides
autophosphorylation, which of the following steps
would be inhibited by Lapatinib?
a. Signaling molecule binding,
dimerization, and the downstream
cellular response.
b. Dimerization, and the downstream
cellular response.
c. The downstream cellular response.
2.
d. Phosphatase activity, dimerization, and
the downsteam cellular response.
Figure 9.10 In certain cancers, the GTPase
activity of the RAS G-protein is inhibited. This
means that the RAS protein can no longer
hydrolyze GTP into GDP. What effect would this
have on downstream cellular events?
3. Figure 9.17 Which of the following statements
about quorum sensing is false?
a. Autoinducer must bind to receptor to
turn on transcription of genes
responsible for the production of more
autoinducer.
b. The receptor stays in the bacterial cell,
but the autoinducer diffuses out.
278 CHAPTER 9 | CELL COMMUNICATION
c. Autoinducer can only act on a different
cell: it cannot act on the cell in which it
is made.
d. Autoinducer turns on genes that enable
the bacteria to form a biofilm.
Figure 9.18 What advantage might biofilm
production confer on the S. aureus inside the
catheter?
4.
REVIEW QUESTIONS
5. What property prevents the ligands of cellsurface receptors from entering the cell?
a. The molecules bind to the extracellular
domain.
b. The molecules are hydrophilic and
cannot penetrate the hydrophobic
interior of the plasma membrane.
c. The molecules are attached to transport
proteins that deliver them through the
bloodstream to target cells.
d. The ligands are able to penetrate the
membrane and directly influence gene
expression upon receptor binding.
d. They are the cleavage products of the
inositol phospholipid, PIP2.
10. What property enables the residues of the
amino acids serine, threonine, and tyrosine to be
phosphorylated?
a. They are polar.
b. They are non-polar.
c. They contain a hydroxyl group.
d. They occur more frequently in the
amino acid sequence of signaling
proteins.
11. What is the function of a phosphatase?
a. A phosphatase removes phosphorylated
amino acids from proteins.
b. A phosphatase removes the phosphate
group from phosphorylated amino acid
residues in a protein.
c. A phosphatase phosphorylates serine,
threonine, and tyrosine residues.
d. A phosphatase degrades second
messengers in the cell.
6. The secretion of hormones by the pituitary
gland is an example of
.
a.
b.
c.
d.
autocrine signaling
paracrine signaling
endocrine signaling
direct signaling across gap junctions
7. Why are ion channels necessary to transport
ions into or out of a cell?
a. Ions are too large to diffuse through the
membrane.
b. Ions are charged particles and cannot
diffuse through the hydrophobic interior
of the membrane.
c. Ions do not need ion channels to move
through the membrane.
d. Ions bind to carrier proteins in the
bloodstream, which must be removed
before transport into the cell.
12. How does NF-κB induce gene expression?
a. A small, hydrophobic ligand binds to
NF-κB, activating it.
b. Phosphorylation of the inhibitor Iκ-B
dissociates the complex between it and
NF-κB, and allows NF-κB to enter the
nucleus and stimulate transcription.
c. NF-κB is phosphorylated and is then
free to enter the nucleus and bind DNA.
d. NF-κB is a kinase that phosphorylates a
transcription factor that binds DNA and
promotes protein production.
8. Endocrine signals are transmitted more slowly
than paracrine signals because
.
a. the ligands are transported through the
bloodstream and travel greater distances
b. the target and signaling cells are close
together
c. the ligands are degraded rapidly
d. the ligands don't bind to carrier proteins
during transport
9. Where do DAG and IP3 originate?
a. They are formed by phosphorylation of
cAMP.
b. They are ligands expressed by signaling
cells.
c. They are hormones that diffuse through
the plasma membrane to stimulate
protein production.
13. Apoptosis can occur in a cell when the cell is
.
a. damaged
b. no longer needed
c. infected by a virus
d. all of the above
14. What is the effect of an inhibitor binding an
enzyme?
a. The enzyme is degraded.
b. The enzyme is activated.
c. The enzyme is inactivated.
d. The complex is transported out of the
cell.
15. Which type of molecule acts as a signaling
molecule in yeasts?
a. steroid
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CHAPTER 9 | CELL COMMUNICATION 279
b. autoinducer
c. mating factor
d. second messenger
b. bacteria release growth hormones
c. bacterial protein expression is switched
on
d. a sufficient number of bacteria are
present
16. Quorum sensing is triggered to begin when
.
a. treatment with antibiotics occurs
CRITICAL THINKING QUESTIONS
17. What is the difference between intracellular
signaling and intercellular signaling?
18. How are the effects of paracrine signaling
limited to an area near the signaling cells?
19. What are the differences between internal
receptors and cell-surface receptors?
20. Cells grown in the laboratory are mixed with a
dye molecule that is unable to pass through the
plasma membrane. If a ligand is added to the cells,
observations show that the dye enters the cells.
What type of receptor did the ligand bind to on the
cell surface?
21. The same second messengers are used in
many different cells, but the response to second
messengers is different in each cell. How is this
possible?
22. What would happen if the intracellular
domain of a cell-surface receptor was switched
with the domain from another receptor?
23. What is a possible result of a mutation in a
kinase that controls a pathway that stimulates cell
growth?
24. How does the extracellular matrix control the
growth of cells?
25. What characteristics make yeasts a good
model for learning about signaling in humans?
26. Why is signaling in multicellular organisms
more complicated than signaling in single-celled
organisms?